The Effect of the Water Drinking Test on Ocular Parameters and Choroidal Thickness in Glaucoma Suspects.

Background and objectives: We aimed to evaluate the effects of the water drinking test (WDT) on several systemic and ocular parameters, including choroidal thickness, which was assessed through optical coherence tomography angiography (OCTA), in glaucoma suspects. Materials and Methods: A total of 40 eyes from 20 glaucoma suspects without any systemic or ocular diseases were included in this prospective observational study. All the participants undertook the WDT, which required the drinking of 1 L of table water in 5 min. The outcome measures included IOP, systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), mean ocular perfusion pressure (MOPP), ocular pulse amplitude (OPA), and subfoveal and peripapillary choroidal thickness, which were assessed at baseline and at four 15 min intervals after the WDT. Generalized least squares models and mixed model analyses that take into account repeated measurements were used to assess the changes over time of these parameters. Results: All the ocular and systemic parameters showed statistically significant changes at all time points compared to baseline apart from choroidal thickness. The peak changes were an IOP of 20.1 mmHg versus 17.3 mmHg at 45 min, an SBP of 137.6 mmHg versus 125 mmHg at 30 min, a DBP of 95.9 mmHg versus 85.7 mmHg at 15 min, and an MOP of 53.51 mmHg versus 48.89 mmHg at 15 min. Conclusions: Despite elevations in IOP and significant changes in all the assessed systemic parameters, the WDT was not associated with changes in choroidal thickness in glaucoma suspects.

Stbd1 promotes glycogen clustering during endoplasmic reticulum stress and supports survival of mouse myoblasts.

Imbalances in endoplasmic reticulum (ER) homeostasis provoke a condition known as ER stress and activate the unfolded protein response (UPR) pathway, an evolutionarily conserved cell survival mechanism. Here, we show that mouse myoblasts respond to UPR activation by stimulating glycogenesis and the formation of α-amylase-degradable, glycogen-containing ER structures. We demonstrate that the glycogen-binding protein Stbd1 is markedly upregulated through the PERK signalling branch of the UPR pathway and is required for the build-up of glycogen structures in response to ER stress activation. In the absence of ER stress, Stbd1 overexpression is sufficient to induce glycogen clustering but does not stimulate glycogenesis. Glycogen structures induced by ER stress are degraded under conditions of glucose restriction through a process that does not depend on autophagosome-lysosome fusion. Furthermore, we provide evidence that failure to induce glycogen clustering during ER stress is associated with enhanced activation of the apoptotic pathway. Our results reveal a so far unknown response of mouse myoblasts to ER stress and uncover a novel specific function of Stbd1 in this process, which may have physiological implications during myogenic differentiation.This article has an associated First Person interview with the first author of the paper.

Molecular Biologic Milieu in Rhegmatogenous Retinal Detachment and Proliferative Vitreoretinopathy: A Literature Review.

Multiple lines of evidence support an immunologic response along with inflammation to be implicated in the pathophysiology of primary rhegmatogenous retinal detachment (RRD) and the development of proliferative vitreoretinopathy (PVR). The purpose of this review is to provide an update on the signaling molecules in the vitreous and subretinal fluid (SRF) involved in these processes. A detailed literature search was performed in PubMed database until November 2021. We identified all papers referring to inflammatory and immunological mediators in the context of primary RRD and in cases complicated by PVR. We analyzed prospective and retrospective cohort studies and reference lists of the retrieved articles. A comprehensive investigation of immunological and inflammatory responses provides significant evidence for the implication of varying signaling molecules in the pathophysiology of RRD and the development of PVR. The reviewed series has revealed that disruption of the normal equilibrium during these processes may be present in the vitreous and SRF of these eyes. The precise role of cytokines, chemokines, and growth factors in the pathophysiology of these disorders remains to be clearly elucidated. Overall, immunological and inflammatory signaling molecules are widely implicated in both primary RRD and PVR. The reviewed literature indicates that precise knowledge concerning the pathological milieu sheds light on the underlying pathophysiology and potential therapeutic targets and highlights unmet needs to be addressed by future research.

Towards Robustifying Image Classifiers against the Perils of Adversarial Attacks on Artificial Intelligence Systems.

Adversarial machine learning (AML) is a class of data manipulation techniques that cause alterations in the behavior of artificial intelligence (AI) systems while going unnoticed by humans. These alterations can cause serious vulnerabilities to mission-critical AI-enabled applications. This work introduces an AI architecture augmented with adversarial examples and defense algorithms to safeguard, secure, and make more reliable AI systems. This can be conducted by robustifying deep neural network (DNN) classifiers and explicitly focusing on the specific case of convolutional neural networks (CNNs) used in non-trivial manufacturing environments prone to noise, vibrations, and errors when capturing and transferring data. The proposed architecture enables the imitation of the interplay between the attacker and a defender based on the deployment and cross-evaluation of adversarial and defense strategies. The AI architecture enables (i) the creation and usage of adversarial examples in the training process, which robustify the accuracy of CNNs, (ii) the evaluation of defense algorithms to recover the classifiers' accuracy, and (iii) the provision of a multiclass discriminator to distinguish and report on non-attacked and attacked data. The experimental results show promising results in a hybrid solution combining the defense algorithms and the multiclass discriminator in an effort to revitalize the attacked base models and robustify the DNN classifiers. The proposed architecture is ratified in the context of a real manufacturing environment utilizing datasets stemming from the actual production lines.

Assessing safety and success after using bevacizumab, 5-fluorouracil or placebo in primary trabeculectomy. A prospective randomized placebo controlled 1-year follow-up study.

PURPOSE: The aim of this study was to determine whether glaucoma patients after trabeculectomy could benefit more from subconjunctival injections of bevacizumab than 5-FU or placebo. METHODS AND RESULTS: Fifty-one eyes of 51 patients were recruited for primary MMC (0.2 mg/mL for 1 min) augmented trabeculectomy. 17 patients were randomly assigned to receive 1.25 mg (0.05 mL) of bevacizumab augmentation, 21 patients were assigned to receive 0.1 mL of 50 mg/mL 5-FU and 13 patients were assigned to a control group receiving a normal saline injection as a placebo. Initial recruitment included 58 patients, but seven patients had to be excluded from the study for various reasons. Postoperative follow up of IOP and bleb characteristics was carried out at 1 day, 1 week, 3 weeks, 6 weeks, 6 months and 1 year after surgery. All analyses where carried out by two masked clinicians. IOP reduction was statistically significant (p < 0.05) across all three groups between baseline visit and final 1-year postoperative visit. There was no significant difference of the final average IOP values between the three groups. Bleb evaluation was made using the Moorfields bleb grading system (MBGS) after 1 year follow up. Central bleb area was statistically greater in the Bevacizumab group when compared with the 5-FU group but not with the placebo group. The vascularity of the central bleb was significantly different between the groups with the Bevacizumab group showing the least vascularity. Vascularity of the peripheral bleb was also decreased in the Bevacizumab group when compared with the placebo group but not with the 5-FU group. CONCLUSION: The 12-month IOP results showed no significant differences between the groups of patients after Bevacizumab, 5-FU or placebo to augment primary MMC enhanced trabeculectomy. However, by the analysis of bleb morphology there was a significant difference in terms of central bleb area and vascularity.

When the Balance Tips: Dysregulation of Mitochondrial Dynamics as a Culprit in Disease.

Mitochondria are dynamic organelles, the morphology of which is tightly linked to their functions. The interplay between the coordinated events of fusion and fission that are collectively described as mitochondrial dynamics regulates mitochondrial morphology and adjusts mitochondrial function. Over the last few years, accruing evidence established a connection between dysregulated mitochondrial dynamics and disease development and progression. Defects in key components of the machinery mediating mitochondrial fusion and fission have been linked to a wide range of pathological conditions, such as insulin resistance and obesity, neurodegenerative diseases and cancer. Here, we provide an update on the molecular mechanisms promoting mitochondrial fusion and fission in mammals and discuss the emerging association of disturbed mitochondrial dynamics with human disease.

Classic galactosaemia in the Greek Cypriot population: An epidemiological and molecular study.

Classic galactosaemia is an inherited metabolic disorder of galactose metabolism caused by deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT) resulting from mutations in the GALT gene. The objectives of the present study were the determination of the carrier frequency of classic galactosaemia in the Greek Cypriot population and the molecular characterization of the disease alleles. We performed an epidemiological study involving 528 Greek Cypriots originating from all parts of Cyprus. Carriers were identified by measuring GALT activity in red blood cells and were subsequently subjected to mutation analysis. A total of five mutations were identified in patients and carriers of classic galactosaemia: a large deletion of 8.5 kb previously reported by us (55% of alleles), the known mutations p.Lys285Asn (30%), p.Pro185Ser (5%), and c.820+13A>G (5%), and a novel mutation c.378-12G>A (5%). Interestingly, the most common mutation in European populations, p.Gln188Arg, was not identified in this Cypriot cohort. The carrier frequency for classic galactosaemia among Greek Cypriots was estimated to be 1:88, predicting a homozygote incidence of 1:31,000 births. The Duarte 1 and Duarte 2 variants were found to be present at a frequency of 5.5% and 2.5%, respectively.

Mouse Stbd1 is N-myristoylated and affects ER-mitochondria association and mitochondrial morphology.

Starch binding domain-containing protein 1 (Stbd1) is a carbohydrate-binding protein that has been proposed to be a selective autophagy receptor for glycogen. Here, we show that mouse Stbd1 is a transmembrane endoplasmic reticulum (ER)-resident protein with the capacity to induce the formation of organized ER structures in HeLa cells. In addition to bulk ER, Stbd1 was found to localize to mitochondria-associated membranes (MAMs), which represent regions of close apposition between the ER and mitochondria. We demonstrate that N-myristoylation and binding of Stbd1 to glycogen act as major determinants of its subcellular targeting. Moreover, overexpression of non-myristoylated Stbd1 enhanced the association between ER and mitochondria, and further induced prominent mitochondrial fragmentation and clustering. Conversely, shRNA-mediated Stbd1 silencing resulted in an increase in the spacing between ER and mitochondria, and an altered morphology of the mitochondrial network, suggesting elevated fusion and interconnectivity of mitochondria. Our data unravel the molecular mechanism underlying Stbd1 subcellular targeting, support and expand its proposed function as a selective autophagy receptor for glycogen and uncover a new role for the protein in the physical association between ER and mitochondria.

Efficacy and safety of dexamethasone intravitreal implant in patients with retinal vein occlusion resistant to anti-VEGF therapy: a 12-month prospective study.

Purpose: To evaluate the safety and efficacy of repeated intravitreal dexamethasone implant (Ozurdex) injections administrated on an "as-needed" protocol for retinal vein occlusion patients with macular oedema, previously subjected to at least five anti-vascular endothelial growth factor (VEGF) injections with poor or no response. Methods: Prospective interventional case series of 13 branch retinal vein occlusion (BRVO) and 10 central retinal vein occlusion (CRVO) patients with persistent macular oedema (>250 µm) after at least five anti-VEGF injections. Exclusion criteria included: baseline visual acuity worse than 1.5 logMAR, previous intravitreal implant, history of vitreoretinal surgery, manifest glaucoma or ocular hypertension, epiretinal membrane, retinal neovascularization, massive retinal or macular ischaemia, vitreous haemorrhage or severe lens opacity, previous laser photocoagulation treatment. Each patient received an initial intraocular dexamethasone implant and the procedure was repeated at 6 months "as needed." Patients were followed up at months 2, 4, 6, 8, 10 and 12 with spectral domain optical coherence tomography and best corrected visual acuity measurements. Exclusion criteria included: baseline visual acuity worse than 1.5 logMAR, previous intravitreal implant, history of vitreoretinal surgery, manifest glaucoma or ocular hypertension, epiretinal membrane, retinal neovascularization, retinal or macular ischaemia, vitreous haemorrhage or severe lens opacity, previous laser photocoagulation treatment. Patients on topical or systemic corticosteroid therapy (during the last 3 months), and known steroid responders as well as diabetic patients were also excluded. Results: In the BRVO group, the mean central retinal thickness (CRT) and best corrected visual acuity (BCVA) significantly improved from 482.92 ± 139.99 µm (0.55 ± 0.12 logMAR) at baseline, to 369.31 ± 119.72 µm (0.43 ± 0.18 logMAR) at 6 months (p = 0.011/p = 0.019). At 12 months CRT was 295.82 ± 135.48 µm (p = 0.026) and BCVA 0.29 ± 0.17 logMAR (p = 0.002). Minimum CRT values were achieved at 3.45 months after the first injection, and 2.46 months after the second injection (197.00 ± 84.27 and 180.00 ± 76.89 µm, respectively). Best BCVA values were achieved at a mean of 4 ± 0.853 months after the first injection, and 4 months after the second injection (0.219 ± 0.129 and 0.222 ± 0.078 logMAR, respectively). In the CRVO group, neither the mean CRT nor BCVA improved significantly at 6 months: from 669.70 ± 203.20 µm (0.80 ± 0.231 logMAR) at baseline, to 586.20 ± 237.63 µm (0.740 ± 0.268 logMAR) at 6 months (p = 0.131/p = 0.333). At 12 months CRT was significantly improved: 549.90 ± 191.26 µm (p = 0.047), but BCVA lacked significant improvement: 0.690 ± 0.285 logMAR (p = 0.072). Minimum CRT values were achieved at a mean of 2 months after the first injection, and also 2 months after the second injection (261.60 ± 121.31 and 280.00 ± 177.43 µm, respectively). Best BCVA values were achieved at a mean of 2 months after the first injection, and 2 months after the second injection and were 0.390 ± 0.173 and 0.385 ± 0.233 logMAR, respectively. Cataract progression was a rare event (2/23 eyes), while transient steroid-induced ocular hypertension (5/23 eyes) was managed successfully with IOP-lowering medication Conclusion: Dexamethasone implant should be considered as an effective and safe alternative in patients with BRVO and CRVO who have failed anti-VEGF therapy. Shortening the re-injection interval especially for CRVO cases should be considered.

A Study of the Natural History of Vitreomacular Traction Syndrome by OCT.

PURPOSE: To examine the natural history of vitreomacular traction syndrome (VMTS) in the absence of other ocular comorbidities. DESIGN: Retrospective clinical case series. PARTICIPANTS: A total of 183 eyes of 159 patients diagnosed with VMTS with no other ocular comorbidity. METHODS: Patients with VMTS were identified from an OCT database at Moorfields Eye Hospital, London. Sequential OCT scans and patient notes were reviewed over a minimum period of 6 months. Data collected included patient demographics, best-corrected visual acuity, and OCT features of vitreomacular adhesion. Contingency tests and binary logistic modeling were used to identify baseline predictors of stability and progression. MAIN OUTCOME MEASURES: The rates of spontaneous resolution (defined by release of traction), progression to full-thickness macular hole, and surgical intervention were analyzed. RESULTS: Presenting visual acuity was 0.3±0.3 logMAR units. The mean length of follow-up was 17.4±12.1 months. During this period, VMTS persisted in 60% and resolved in 20% (occurring on average at 15 months). Of the remainder, 12% developed a macular hole and 8% elected to proceed with surgery for symptoms. Focal adhesion <1500 µm was present in 87%. A premacular membrane with macular pucker (PMM) was present in 20%. With persistent VMTS, vision and central foveal thickness remained unchanged. The relative risk of resolution increased in those cases with better presenting visual acuities, lesser foveal thicknesses, and no associated PMMs; vision significantly improved in those cases with resolution. CONCLUSIONS: VMTS persists in the majority of patients but despite this, visual acuities did not deteriorate significantly over the study period unless patients developed a full-thickness macular hole or required surgical intervention for symptoms. Resolution spontaneously occurred in 20%, with an improvement in vision.

PARS PLANA VITRECTOMY AND LENSECTOMY FOR ECTOPIA LENTIS WITH AND WITHOUT THE INDUCTION OF A POSTERIOR VITREOUS DETACHMENT.

PURPOSE: Posterior hyaloid removal during pars plana vitrectomy and lensectomy for ectopia lentis is commonly performed, but may increase the risk of intraoperative retinal breaks and postoperative retinal detachment. This study evaluated outcomes after pars plana vitrectomy and lensectomy with or without posterior hyaloid removal. METHODS: This retrospective observational cohort study included ectopia lentis cases that underwent pars plana vitrectomy and lensectomy (2005-2014), with or without intraoperative induction of a posterior vitreous detachment (PVD). The primary outcome was postoperative retinal detachment. The secondary outcomes were the incidence of iatrogenic retinal breaks, and change in visual acuity. RESULTS: Twenty-six cases were included. The posterior hyaloid was preserved intraoperatively in 11 cases (non-PVD group). In the remainder (15 cases), the vitreous was removed completely (PVD group). Postoperative retinal detachment occurred in 2 cases in each group (18.2% non-PVD vs.13.3% PVD, P = 0.7). Intraoperative breaks occurred more frequently in the PVD group (2 vs. 9 cases; P = 0.03). There was no difference in mean improvement in visual acuity (7 [PVD] vs. 3 [non-PVD] ETDRS lines; P = 0.2). CONCLUSION: The preservation of posterior hyaloid attachment during vitreolensectomy for ectopia lentis was associated with fewer iatrogenic retinal breaks. Postoperative retinal detachment did not seem to be influenced by the choice of surgical technique.

Supradescemetic voriconazole injection for Candida parapsilosis keratitis.

PURPOSE: To describe a technique for intracorneal application of voriconazole into the supradescemetic space in a case of deep recalcitrant Candida parapsilosis keratitis of a penetrating cornea graft. METHODS: A deep intracorneal incision reaching the center of the corneal infiltrate was created with a 20-gauge MVR blade. Then, a 27-gauge hydrodissection cannula was inserted deep into the corneal pocket, and 0.1 ml of voriconazole 0.5 mg/ml was injected until a bullous detachment of Descemet membrane (DM) covered 1/3 of the graft's area. DM detachment was documented by anterior segment optical coherence tomography (AS-OCT). RESULTS: AS-OCT confirmed the creation of a drug depot in the supradescemetic space, which partially regressed during the following hours; 24 h after the injection, a complete reattachment of DM was documented. After 4 weeks, the stromal infiltrate has cleared completely and no signs of recurrence were observed 3 months after injection. CONCLUSION: In the present case, the supradescemetic voriconazole injection led to resolution of a deep recalcitrant fungal infiltrate. The herein described technique could be tried in similar cases, where an intrastromal injection is indicated, as it may offer a larger intracorneal drug depot.

CAPILLARY NONPERFUSION AND PHOTORECEPTOR LOSS IN BRANCH RETINAL VEIN OCCLUSION: Spatial Correlation and Morphologic Characteristics.

PURPOSE: To evaluate the photoreceptor layer in eyes with branch retinal vein occlusion associated with macular ischemia, using a method of en face optical coherence tomography (OCT) representation of the ellipsoid zone. METHODS: Customized macular OCT scans of 9 patients (10 eyes) with branch retinal vein occlusion and macular ischemia were exported and subsequently postprocessed (removal of vascular and cystic spaces' shadows, segmentation, and alignment to the retinal pigment epithelium). The ellipsoid band was then isolated, aligned, and used to produce an en face OCT image. Areas with photoreceptor loss (hyporeflective ellipsoid) were compared with ischemic areas as identified in an early-phase fluorescein angiography. RESULTS: The areas of capillary nonperfusion (as detected in fluorescein angiography) were closely associated with disruption of the ellipsoid zone (depicted as areas of low reflectance in the en face reconstruction of the OCT images). The ellipsoid zone disruption had a patchy appearance and either sharp or fuzzy borders, depending on the grade of the loss of reflectance. CONCLUSION: En face OCT reconstruction and subsequent representation of ellipsoid zone revealed a close association between capillary nonperfusion and photoreceptor disruption in eyes with branch retinal vein occlusion. It seems that the deep capillary plexus plays an important role on the metabolic demands of outer retina and, consequently, an ischemia at the level of deep capillary plexus has significant impact on the integrity of the photoreceptors.

Early anti-VEGF treatment for hemorrhagic occlusive retinal vasculitis as a complication of cataract surgery.

BACKGROUND: We report a case of hemorrhagic occlusive retinal vasculitis (HORV) after prophylactic intracameral vancomycin use during an uneventful cataract surgery treated with early anti-VEGF treatment. CASE PRESENTATION: A 51-year-old female underwent uneventful cataract surgery with prophylactic intracameral vancomycin during the procedure. On the seventh post-operative-day, she presented with sudden painful, visual loss. Fundus examination revealed peripheral hemorrhagic retinal vasculitis. She received anti-VEGF therapy to prevent further vision loss and retinal neovascularization due to extensive retinal ischemia. At the 6-month follow-up visit, visual acuity was 20/20 with no sign of neovascularization. CONCLUSIONS: Postoperative HORV is a devastating condition that can occur after otherwise uncomplicated cataract surgery. The nature of this rare condition remains unknown. Early anti-VEGF administration seems to demonstrate favorable results.

Bleb failure and intraocular pressure rise following Nd: Yag laser capsulotomy.

BACKGROUND: To report the negative effect of Nd: Yag (Neodymium-doped: Yttrium Aluminium Garnet) laser capsulotomy on the intraocular pressure (IOP) and the trabeculectomy bleb integrity, in a small series of eyes, both trabeculectomised and pseudophakic, following the laser application for the management of posterior capsular opacification (PCO). METHODS: This is a retrospective, non-comparative interventional case series study, in which 20 trabeculectomised and pseudophakic eyes from 15 patients, with otherwise well functioning blebs, were presented with uncontrolled IOP, in a variable distance of time following the application of YAG laser capsulotomy. Student paired t-test confirmed a statistically significant difference (P < 0.05) between IOP before Nd: YAG laser capsulotomy (16 mmHg ± 3 mmHg) and the respective one, 2 to 6 months after Nd: Yag capsulotomy (34.5 ± 11 mmHg). RESULTS: All of the cases failed to respond to conservative treatment and were successfully managed with the implantation of Ahmed drainage devices. All patients showed flat filtering bleb and uncontrolled IOP (34.5 ± 11 mmHg), under maximum topical treatment, in a period of 2 to 6 months following Nd: YAG laser caspulotomy. The implantation of Ahmed valve proved to be effective treatment for these patients (IOP < 21 mmHg). CONCLUSIONS: Although Nd: Yag laser capsulotomy is considered a safe surgical procedure and usually is done without second thought, in this series of eyes, it is postulated that it may be responsible for the deregulation of the filtering bleb and subsequent loss of IOP control. We consider that laser capsulotomy should be performed with caution, especially in eyes with previous trabeculectomy. Also close monitoring of the intraocular pressure and assessment of eventual bleb morphology variations in the follow-up period is mandatory. Further studies are needed in order to confirm our findings.

EXTENT AND LOCATION OF INTRARETINAL AND SUBRETINAL FLUID AS PROGNOSTIC FACTORS FOR THE OUTCOME OF PATIENTS WITH OPTIC DISK PIT MACULOPATHY.

PURPOSE: To determine if baseline fundoscopic and optical coherence tomography (OCT) features influence the clinical course of optic disk pit maculopathy. METHODS: A multicenter retrospective case note review was undertaken, using standardized OCT and clinical data collection. Visual success was defined as at least a two-line visual acuity improvement, anatomical success as full resolution of OCT foveal fluid with restoration of the normal foveal contour, and partial anatomical success as incomplete resolution of the OCT foveal fluid. Outcomes were compared with a synthesis of the literature, using similar eligibility criteria. RESULTS: Of 36 patients (36 eyes), 2 spontaneously improved and 34 underwent surgery. Visual success was achieved in 64% of surgical cases, anatomical success in 36%, and partial anatomical success in 47%. Cases with multilayer intraretinal and subretinal fluid were less likely to have visual success (P = 0.003). Cases where the fluid did not extend to the macular arcade vessels also had better visual and anatomical outcomes (P = 0.004 and 0.005, respectively). CONCLUSION: Fundoscopic and OCT features can help predict surgical outcome in optic disk pit maculopathy.

Case report: Aqueous and Vitreous amino-acid concentrations in a patient with maple syrup urine disease operated on rhegmatogenous retinal detachment.

BACKGROUND: Maple syrup urine disease (MSUD) is a rare metabolic disorder, affecting the metabolism of branched chain amino-acids (Valine, Leukine, Isoleukine). We present a rare case of rhegmatogenous retinal detachment (RRD) in a MSUD patient. CASE PRESENTATION: We performed amino acid analysis of aqueous humour, vitreous and serum samples obtained during surgery from a 24 year old female MSUD patient successfully operated on RRD. Serum values for a-amino-butyric acid, valine, isoleucine, leucine, tyrosine, phenylalanine, ornithine and histidine were low, while values for citrulline, methionine and lysine were borderline low, all attributed to the patient's special diet. Serum glutamate was above normal, probably due to the breakdown of glutamine to glutamate. In the aqueous and vitreous the amino acids implicated in MSUD (Valine, Leukine Isoleukine), were within normal range. Glutamate was absent in the vitreous and presented low levels in the aqueous. Glutamate has been reported to play an important role in retinal damage. Elevated glutamate levels have been reported in vitreous specimens from patients subjected to vitrectomy or buckling surgery for RRD. In MSUD, glutamate has been implicated in the pathogenesis of brain damage. Low levels of glutamate have been observed in the cerebellum of experimental MSUD animals, as well as postmortem brain tissue from a child that died of leucine intoxication. The reduction was attributed to the elevation of a-ketoisocaproic which reverses the net direction of nitrogen flow. It could be argued that this could impact on amino acid concentration in aqueous and vitreous fluids. CONCLUSIONS: Although no definite conclusions can be drawn by this extremely rare case, the low vitreous and aqueous levels of Glutamate is an interesting finding. Further studies are needed to provide a better insight in the role of amino acids as neurotransmitters in the human eye in health and disease.